Devices for maintaining patency of surgically created channels in tissue

ABSTRACT

Devices and methods for altering gaseous flow within a lung to improve the expiration cycle of an individual, particularly individuals having chronic obstructive pulmonary disease. The methods and devices create channels in lung tissue and maintain the patency of these surgically created channels in tissue. Maintaining the patency of the channels allows air to pass directly out of the lung tissue which facilitates the exchange of oxygen ultimately into the blood and/or decompresses hyper-inflated lungs.

REFERENCE TO RELATED APPLICATION

This application is a continuation of International Application NumberPCT/US2004/023304 filed Jul. 19, 2004 which claims the benefit under 35U.S.C. §119(e) of Provisional Application No. 60/488,332 filed Jul. 18,2003, the contents of which are incorporated herein in their entirety.

FIELD OF THE INVENTION

This is directed to methods and devices for altering gaseous flow withina lung to improve the expiration cycle of an individual, particularlyindividuals having chronic obstructive pulmonary disease. The methodsand devices create channels in lung tissue and maintain the patency ofthese surgically created channels in tissue. Maintaining the patency ofthe channels allows air to pass directly out of the lung tissue whichfacilitates the exchange of oxygen ultimately into the blood and/ordecompresses hyper-inflated lungs.

BACKGROUND OF THE INVENTION

The American Lung Association (ALA) estimates that nearly 16 millionAmericans suffer from chronic obstructive pulmonary disease (COPD) whichincludes diseases such as chronic bronchitis, emphysema, and some typesof asthma. The ALA estimated that COPD was the fourth-ranking cause ofdeath in the U.S. The ALA estimates that about 14 million and 2 millionAmericans suffer from emphysema and chronic bronchitis respectively.

Those inflicted with COPD face disabilities due to the limited pulmonaryfunctions. Usually, individuals afflicted by COPD also face loss inmuscle strength and an inability to perform common daily activities.Often, those patients desiring treatment for COPD seek a physician at apoint where the disease is advanced. Since the damage to the lungs isirreversible, there is little hope of recovery. Most times, thephysician cannot reverse the effects of the disease but can only offertreatment and advice to halt the progression of the disease.

To understand the detrimental effects of COPD, the workings of the lungsrequires a cursory discussion. The primary function of the lungs is topermit the exchange of two gasses by removing carbon dioxide fromarterial blood and replacing it with oxygen. Thus, to facilitate thisexchange, the lungs provide a blood gas interface. The oxygen and carbondioxide move between the gas (air) and blood by diffusion. Thisdiffusion is possible since the blood is delivered to one side of theblood-gas interface via small blood vessels (capillaries). Thecapillaries are wrapped around numerous air sacs called alveoli whichfunction as the blood-gas interface. A typical human lung contains about300 million alveoli.

The air is brought to the other side of this blood-gas interface by anatural respiratory airway, hereafter referred to as a natural airway orairway, consisting of branching tubes which become narrower, shorter,and more numerous as they penetrate deeper into the lung. Specifically,the airway begins with the trachea which branches into the left andright bronchi which divide into lobar, then segmental bronchi.Ultimately, the branching continues down to the terminal bronchioleswhich lead to the alveoli. Plates of cartilage may be found as part ofthe walls throughout most of the airway from the trachea to the bronchi.The cartilage plates become less prevalent as the airways branch.Eventually, in the last generations of the bronchi, the cartilage platesare found only at the branching points. The bronchi and bronchioles maybe distinguished as the bronchi lie proximal to the last plate ofcartilage found along the airway, while the bronchiole lies distal tothe last plate of cartilage. The bronchioles are the smallest airwaysthat do not contain alveoli. The function of the bronchi and bronchiolesis to provide conducting airways that lead air to and from the gas-bloodinterface. However, these conducting airways do not take part in gasexchange because they do not contain alveoli. Rather, the gas exchangetakes place in the alveoli which are found in the distal most end of theairways.

The mechanics of breathing include the lungs, the rib cage, thediaphragm and abdominal wall. During inspiration, inspiratory musclescontract increasing the volume of the chest cavity. As a result of theexpansion of the chest cavity, the pleural pressure, the pressure withinthe chest cavity, becomes sub-atmospheric. Consequently, air flows intothe lungs and the lungs expand. During unforced expiration, theinspiratory muscles relax and the lungs begin to recoil and reduce insize. The lungs recoil because they contain elastic fibers that allowfor expansion, as the lungs inflate, and relaxation, as the lungsdeflate, with each breath. This characteristic is called elastic recoil.The recoil of the lungs causes alveolar pressure to exceed atmosphericpressure causing air to flow out of the lungs and deflate the lungs. ‘Ifthe lungs’ ability to recoil is damaged, the lungs cannot contract andreduce in size from their inflated state. As a result, the lungs cannotevacuate all of the inspired air.

In addition to elastic recoil, the lung's elastic fibers also assist inkeeping small airways open during the exhalation cycle. This effect isalso known as “tethering” of the airways. Tethering is desirable sincesmall airways do not contain cartilage that would otherwise providestructural rigidity for these airways. Without tethering, and in theabsence of structural rigidity, the small airways collapse duringexhalation and prevent air from exiting thereby trapping air within thelung.

Emphysema is characterized by irreversible biochemical destruction ofthe alveolar walls that contain the elastic fibers, called elastin,described above. The destruction of the alveolar walls results in a dualproblem of reduction of elastic recoil and the loss of tethering of theairways. Unfortunately for the individual suffering from emphysema,these two problems combine to result in extreme hyperinflation (airtrapping) of the lung and an inability of the person to exhale. In thissituation, the individual will be debilitated since the lungs are unableto perform gas exchange at a satisfactory rate.

One further aspect of alveolar wall destruction is that the airflowbetween neighboring air sacs, known as collateral ventilation orcollateral air flow, is markedly increased as when compared to a healthylung. While alveolar wall destruction decreases resistance to collateralventilation, the resulting increased collateral ventilation does notbenefit the individual since air is still unable to flow into and out ofthe lungs. Hence, because this trapped air is rich in CO₂, it is oflittle or no benefit to the individual.

Chronic bronchitis is characterized by excessive mucus production in thebronchial tree. Usually there is a general increase in bulk(hypertrophy) of the large bronchi and chronic inflammatory changes inthe small airways. Excessive amounts of mucus are found in the airwaysand semisolid plugs of this mucus may occlude some small bronchi. Also,the small airways are usually narrowed and show inflammatory changes.

Currently, although there is no cure for COPD, treatment includesbronchodilator drugs, and lung reduction surgery. The bronchodilatordrugs relax and widen the air passages thereby reducing the residualvolume and increasing gas flow permitting more oxygen to enter thelungs. Yet, bronchodilator drugs are only effective for a short periodof time and require repeated application. Moreover, the bronchodilatordrugs are only effective in a certain percentage of the population ofthose diagnosed with COPD. In some cases, patients suffering from COPDare given supplemental oxygen to assist in breathing. Unfortunately,aside from the impracticalities of needing to maintain and transport asource of oxygen for everyday activities, the oxygen is only partiallyfunctional and does not eliminate the effects of the COPD. Moreover,patients requiring a supplemental source of oxygen are usually neverable to return to functioning without the oxygen.

Lung volume reduction surgery is a procedure which removes portions ofthe lung that are over-inflated. The portion of the lung that remainshas relatively better elastic recoil, providing reduced airwayobstruction. The reduced lung volume also improves the efficiency of therespiratory muscles. However, lung reduction surgery is an extremelytraumatic procedure which involves opening the chest and thoracic cavityto remove a portion of the lung. As such, the procedure involves anextended recovery period. Hence, the long term benefits of this surgeryare still being evaluated. In any case, it is thought that lungreduction surgery is sought in those cases of emphysema where only aportion of the lung is emphysematous as opposed to the case where theentire lung is emphysematous. In cases where the lung is only partiallyemphysematous, removal of a portion of emphysematous lung which wascompressing healthier portions of the lung allows the healthier portionsto expand, increasing the overall efficiency of the lung. If the entirelung is emphysematous, however, removal of a portion of the lung removesgas exchanging alveolar surfaces, reducing the overall efficiency of thelung. Lung volume reduction surgery is thus not a practical solution fortreatment of emphysema where the entire lung is diseased.

Both bronchodilator drugs and lung reduction surgery fail to capitalizeon the increased collateral ventilation taking place in the diseasedlung. There remains a need for a medical procedure that can alleviatesome of the problems caused by COPD. There is also a need for a medicalprocedure that alleviates some of the problems caused by COPDirrespective of whether a portion of the lung, or the entire lung isemphysematous. The production and maintenance of collateral openingsthrough an airway wall allows air to pass directly out of the lungtissue responsible for gas exchange. These collateral openings serve todecompress hyper inflated lungs and/or facilitate an exchange of oxygeninto the blood.

It was found that creation of collateral channels in COPD patientsallowed expired air to pass out of the lungs and decompressedhyper-inflated lungs. Such methods and devices for creating andmaintaining collateral channels are discussed in U.S. patent applicationSer. No. 09/633,651, filed on Aug. 7, 2000; U.S. patent application Ser.Nos. 09/947,144, 09/946,706, and 09/947,126 all filed on Sep. 4, 2001;U.S. Provisional Application No. 60/317,338 filed on Sep. 4, 2001; U.S.Provisional Application No. 60/334,642 filed on Nov. 29, 2001; U.S.Provisional Application No. 60/367,436 filed on Mar. 20, 2002; and U.S.Provisional Application No. 60/374,022 filed on Apr. 19, 2002 each ofwhich is incorporated by reference herein in its entirety.

It was found that creating an opening/channel through an airway wallovercomes the shortcomings associated with bronchodilator drugs and lungvolume reduction surgery. To further improve the benefit provided by thechannel a need further remains to extend the duration of which thechannel remains open (e.g., patency of the opening). Surgically creatinga hole in tissue triggers a healing cascade. The body's natural healingresponse sets into motion, amongst other things, cell proliferationwhich can result in a build-up of scar tissue. This tissue overgrowthcan occlude or otherwise close the surgically created opening.Additionally, in the event an implant is deployed in the surgicallycreated opening to maintain the patency of the opening, the implant maybecome encapsulated or filled with tissue thereby occluding the channel.

Drug eluting coronary-type stents are not known to overcome the abovementioned events because these stents are often substantiallycylindrical (or otherwise have a shape that conforms to the shape of atubular blood vessel). Hence, they may slide and eject from surgicallycreated openings in an airway wall leading to rapid closure of anychannel. Additionally, the design and structure of the coronary-typestents reflect the fact that these stents operate in an environment thatcontains different tissues when compared to the airways not to mentionan environment where there is a constant flow of blood against thestent. Moreover, the design of coronary stents also acknowledges theneed to avoid partial re-stenosis of the vessel after stent placement.In view of the above, implants suited for placement in the coronary areoften designed to account for factors that may be insignificant whenconsidering a device for the airways.

Not surprisingly, experiments in animal models found that placement of apaclitaxel drug eluting vascular stent into the opening did not yieldpositive results in maintaining the patency of the opening. Theshortcomings were both in the physical structure of the stent along withthe failure to control the healing cascade caused by creation of thechannel.

An understanding of the distinctions between the healing response in thecoronary versus the airways may explain this outcome. For purposes ofour discussion, the healing response in both the coronary and the lungsmay be divided into approximately four stages as measured relative tothe time of the injury: 1) acute phase; 2) sub-chronic phase; 3) chronicphase; and 4) late phase.

In the coronary, after trauma caused by the placement of a coronarystent, the healing process begins in the acute phase with thrombus andacute inflammation. During the sub-chronic phase, there is anorganization of the thrombus, an acute/chronic inflammation and earlyneointima hyperplasia. In the following chronic phase, there is aproliferation of smooth muscle cells along with chronic inflammation andadventitial thickening. In the late stage of the healing process thereis chronic inflammation, neointimal remodeling, medial hypertrophy andadventitial thickening. Based upon the observations in a rabbit model,the healing response in the airway begins with a fibrinous clot, edemahemorrhage, and fibrin deposition. In the sub-chronic phase there isre-epithelialization, mucosal hypertrophy, squamous metaplasia,fibroplasias and fibrosus. In the chronic phase, while the epithelium isintact and there is less mucosal hypertrophy, there is still fibroplasiaand fibrosis. In the late stage the respiratory epithelium is intact andthere is evidence of a scar.

In view of the above, a need remains to create channels in airways ofCOPD patients. A need also remains for methods and devices for creatingthe channels and placing conduits therein such that the patency of theopening is extended.

SUMMARY OF THE INVENTION

The invention includes methods and devices for treating a lung suspectedof having chronic obstructive pulmonary disease through the creation ofcollateral channels. The invention also includes extending the durationduring which these channels remain open (e.g., maintaining patency.)

In one variation, the invention includes a method comprising selecting atreatment site in an airway of the lung, creating a hole in an airwaywall of the airway; and expanding the hole in the airway wall.

Selecting the treatment site may include visual inspection of the siteor inspection for the presence or absence of a blood vessel underneaththe surface of the airway wall.

Selection of the site may be performed or aided by non-invasive imaging.Such imaging may include x-ray, ultrasound, Doppler, acoustic, MRI, PET,and computed tomography (CT) scans. Furthermore, a substance may beadministered into the lungs to assist in the selection of the treatmentsite. For example, the substance may comprise a hyperpolarized gas, athermochromatic dye, a regular dye, and/or a contrast agent.

Variations of the invention include the use of a less-traumaticholemaker for creation of the channel (note that a channel includes ahole that is created and subsequently expanded.) The less traumaticholemaker may include a piercing member (e.g., a needle, a cannula, ablade, a tube, a rod or other similar structure). The less traumaticholemaker may also include devices which minimize the collateral damageto tissue (e.g., low temperature RF devices, pulsating RF, lowtemperature laser, ultrasound, high pressure water, etc.)

In particular, the devices and methods prevent closure of the channelsuch that air may flow through the channel and into the airway. Suchchannels may be made by a variety of methods as discussed in the patentsincorporated by reference above. For example, the channel may be madevia a surgical incision, a needle, a rotary coring device, etc.Furthermore, the channel may be made by an energy based device, e.g., RFdevice, laser, etc. However, it has been noted that use of lowtemperature devices, e.g., mechanical devices, to create the channelresult in less trauma to surrounding tissue and thereby minimize thehealing response of the tissue. Accordingly, such modes of creating thechannel often result in less occlusion of the channel.

The method includes expanding the hole by inserting a conduit into thehole. Furthermore, the method may comprise partially expanding the holeby deploying the conduit in the hole, and then fully expanding the holeby expanding the conduit within the hole.

Preventing closure may be performed using various approaches including,but not limited to, biochemical, electrical, thermal, irradiation, ormechanical approaches (or any combination thereof).

The method may also include delivering a bio-active composition, asdescribed herein, to maintain patency of the channel or conduit. Thebio-active composition may be delivered to the airway wall prior tocreation of the channel, subsequent to creation of the channel, and/orafter insertion and deployment of the conduit. The bio-activecomposition may also be delivered through a drug eluting process, eitherthrough a composition placed on the conduit, or via delivery of aseparate eluting substance.

Biochemical approaches include delivery of medicines that inhibitclosure of the surgically created channel. The medicines may bedelivered locally or systematically. In one variation, a deliverycatheter includes a dispense lumen that sends a drug to the target site.Also, bioactive substances may be delivered to the channel tissue usingvarious delivery vehicles such as a conduit. The bioactive substance maybe disposed on an exterior surface of the conduit such that it interactswith the channel tissue when the conduit is placed at the injury site.Also, bioactive substances may be delivered to the channel tissue beforeor after the conduit is positioned in the channel. The bioactive agentmay also be delivered to the target site alone. That is, a medicine maybe sent to the surgically created channel as the sole mechanism formaintaining the patency of the channel.

Also, systematic delivery of medicines may be carried out throughdigestion, injection, inhalation, etc. Systematic delivery of medicinesmay be provided alone or in combination with other techniques describedherein. For example, a patient having undergone the procedures describedherein may be prescribed steroids and/or COX-2 inhibitors in an attemptto prolong the effects of the treatment.

Any of the conduits discussed herein may also include at least onevisualization feature disposed on a portion of the tissue barrier. Thevisualization feature may be a stripe circumferentially disposed aboutat least a portion of the center section. The visualization featureserves to aid in placement or deployment of the conduit in a targetsite.

Another conduit for maintaining the patency of a channel created intissue comprises a radially expandable center section and extensionmembers as described above. A bioactive substance is disposed on atleast a portion of a surface of the conduit. Also, when the conduit isradially expanded it has an overall length and an inner diameter suchthat a ratio of the overall length to the inner diameter ranges from 1/6to 2/1. The conduit may also be provided such that this ratio rangesfrom 1/4 to 1/1 and perhaps, 1/4 to 1/2. A tissue barrier may bedisposed on at least a portion of the exterior surface corresponding tothe center section. The tissue barrier may be comprised of variousmaterials including but not limited to polymers and elastomers. Anexample of a material which may be used for the tissue barrier issilicone. Additional matrixes of biodegradable polymer and medicines maybe associated with the tissue barrier such that controlled doses ofmedicines are delivered to the tissue opening.

The invention includes a hole-making catheter for creating and dilatingan opening within tissue, the catheter comprising an elongate shafthaving a proximal portion and a distal portion, and at least one lumenextending through the proximal end; a balloon having an interior influid communication with the lumen, the balloon located on the distalportion of the elongate shaft, the balloon having an uninflated stateand an inflated state; a piercing member located at the distal portionof the elongate shaft, the piercing member being extendable andretractable within the elongate shaft; and a depth limiter stop locatedon the exterior of the distal portion of the elongate shaft, proximal tothe balloon and larger in working diameter than the uninflated balloon,which limits the maximum penetration of the catheter into tissue.

The piercing member may include a body portion having a lumen extendingtherethrough. The lumen of the piercing member may be in fluidcommunication with a central lumen of the elongate shaft. In somevariations of the invention an obturator is used within the device,where the obturator is slidably located within the lumen of the elongatebody and piercing member.

The elongate body and/or piercing member may have multiple lumens. Forexample, they may be constructed from multi-lumen tubing. In somevariations, the piercing member is retractable within the elongateshaft.

The balloon member may consist of a distensible balloon or anon-distendsible balloon. For either type of balloon, the workingdiameter may closely match the outer diameter of the piercing member.

The invention may also include an implant located about the balloon ofthe device. In use, the piercing member would create a channel withinthe tissue, the device is then further advanced until the implant islocated within the channel. Inflation of the balloon then deploys theimplant within the channel thereby improving the patency of the channel.

Implants for the present invention include, but are not limited to, astent, conduit, grommet, valve, graft, anchor, etc.

It should be noted that since the device must often access airways deepwithin the lung, the elongate shaft may be comprised of a flexiblematerial. In particular, the elongate shaft may be sufficiently flexibleto pass through a fully articulated bronchoscope.

The piercing member of the current invention may also be used to deliverbio-active agents to the site of the collateral channel. As describedherein, such agents may increase the duration of patency of the channelsand/or implants.

The invention includes a balloon catheter for deploying a device withinan opening in tissue, the balloon catheter comprising an elongate shafthaving a proximal portion, a distal portion, a proximal end, a distalend; and at least one lumen extending through the proximal end, aballoon having an interior in fluid communication with the lumen, theballoon located on the distal end portion of the elongate shaft, a guidemember extending distally from the distal end of the elongate shaft, theguide member comprising a rounded surface at an end opposite to theelongate shaft, where the guide member has sufficient column strength topenetrate the opening in tissue, the guide member further comprising atleast one resistance surface a such that when the body enters theopening, the resistance surface exerts resistance against tissue uponremoval of the guide member from the opening.

The resistance surface may have an increased diameter greater to provideresistance upon removal from tissue. It may alternatively, or incombination, comprise a rough surface to provide added friction uponremoval of the device.

The guide member may be tapered, rounded, partially-spherical,elliptical, prolate, cone-shaped, triangular, or any similar shape. Itis contemplated that there may be more than one resistance surface onthe guide body. Moreover, the guide body may have a wavy/variablediameter shape providing several resistance surfaces on the areas ofincreased diameter.

The device may also be used with an implant that may be located aboutthe balloon where upon expansion of the balloon, the implant deploys.The implant may be selected from a stent, conduit, grommet, valve,graft, and anchor.

In another variation of the invention, the balloon catheter may furthercomprise a dilating member located distally of the balloon. The dilatingmember may be is located on the distal portion of the shaft between thedistal end and the balloon and may comprise a tapered section, a secondballoon, or other similar structure.

In some variations of the invention, the dilating member may beretractable within the elongate shaft.

The device may also include a needle assembly moveably located in theinstrument lumen, where the needle assembly is advanceable through ahole-making lumen and out of the opening in the rounded surface.

The balloon catheter may be constructed to be sufficient flexibility toadvance through a fully articulated bronchoscope.

The balloon catheter may also be configured to deliver bio-activesubstances (e.g., drugs, medicines, compounds, etc.) to the tissue,either via the elongate tube or the guide member. Furthermore, thedevice may be adapted to provide suction to clear the target site.

The invention includes a hole-making catheter for creating and dilatingan opening within tissue, the catheter comprising; an elongate shafthaving a proximal portion and a distal portion, and at least one lumenextending through the proximal end; a nondistensible balloon having aninterior in fluid communication with the lumen, the nondistensibleballoon located on the distal portion of the elongate shaft; and apiercing member located at the distal portion of the elongate shaft, thepiercing member being extendable and retractable within the elongateshaft.

The invention includes an implant delivery system for deploying theimplant within a wall of tissue, the system comprising; an elongateshaft having a distal portion, a proximal end, a distal end, at leastone lumen extending through the proximal end; a balloon member having aninterior in fluid communication with the lumen, the balloon memberlocated on the distal portion of the elongate shaft; a piercing memberdistally located to the distal end of the elongate shaft within thesecond lumen, the solid piercing member having a sharpened distal endadapted to penetrate tissue; and an expandable implant located about theballoon member.

The preceding illustrations are examples of the invention describedherein. It is contemplated that, where possible, combinations offeatures/aspects of specific embodiments or combinations of the specificembodiments themselves are within the scope of this disclosure.

This application is also related to the following applications60/420,440 filed Oct. 21, 2002; 60/387,163 filed Jun. 7, 2002; Ser. No.10/235,240 filed Sep. 4, 2002; Ser. No. 09/947,144 filed Sep. 4, 2001;Ser. No. 09/908,177 filed Jul. 18, 2001; Ser. No. 09/633,651 filed Aug.7, 2000; and 60/176,141 filed Jan. 14, 2000; Ser. No. 10/080,344 filedFeb. 21, 202; Ser. No. 10/079,605 filed Feb. 21, 2002; Ser. No.10/280,851 filed Oct. 25, 2002; and Ser. No. 10/458,085 filed Jun. 9,2003. Each of which is incorporated by reference herein.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A-1C illustrate various states of the natural airways and theblood-gas interface.

FIG. 1D illustrates a schematic of a lung demonstrating a principle ofthe invention described herein.

FIG. 2A illustrates a side view of a conduit in an undeployed state.

FIG. 2B illustrates a side view of the conduit of FIG. 2A shown in adeployed shape.

FIG. 2C illustrates a front view of the conduit shown in FIG. 2B.

FIG. 2D is a cylindrical projection of the undeployed conduit shown inFIG. 2A.

FIG. 2E illustrates a side view of another variation of a conduit in anundeployed shape.

FIG. 2F illustrates a side view of the conduit of FIG. 2E in a deployedstate.

FIG. 2G is a cylindrical projection of the undeployed conduit shown inFIG. 2E.

FIG. 3A illustrates a side view of a conduit having a tissue barrier ina deployed state.

FIG. 3B illustrates a side view of a conduit having a tissue barrier.

FIG. 3C is a front view of the conduit shown in FIG. 3B.

FIG. 3D illustrates a conduit positioned in a channel created in atissue wall.

FIG. 3E is a cross sectional view of the conduit shown in FIG. 3B takenalong line 3E-3E.

FIGS. 3F-3G depict another conduit including a membrane that supports abioactive substance; the bioactive substance may be coated on themembrane.

FIGS. 4A-4C a variation of selecting a site, creating a channel at thesite using a less traumatic hole-maker, and expanding the channel.

FIGS. 4D-4K illustrate variations of piercing members for creatingcollateral channels.

FIGS. 5A-5C illustrate a method for deploying a conduit.

FIGS. 5D-5E illustrate a method for deploying a conduit within anotherimplant.

FIGS. 6A-6B illustrate a method for deploying a conduit at an angle.

FIGS. 7A-7B illustrate placement of a conduit within a channel by usinga guide member.

FIGS. 8A-8F illustrate additional variations of guide bodies for usewith catheters of the present invention.

FIGS. 9A-9B illustrate additional features for use with guide bodies ofthe present invention.

DETAILED DESCRIPTION OF THE INVENTION

Described herein are devices (and methods) for improving the gasexchange in the lung. In particular, methods and devices are describedthat serve to maintain collateral openings or channels through an airwaywall so that air is able to pass directly out of the lung tissue andinto the airways. This facilitates exchange of oxygen into the blood anddecompresses hyper inflated lungs.

By “channel” it is meant to include, but not be limited to, any opening,hole, slit, channel or passage created in the tissue wall (e.g., airwaywall). The channel may be created in tissue having a discrete wallthickness and the channel may extend all the way through the wall. Also,a channel may extend through lung tissue which does not have welldefined boundaries such as, for example, parenchymal tissue.

The channels may be maintained by preventing or inhibiting tissue fromgrowing into or otherwise blocking the channel. Chemical, electrical,light, mechanical, or a combination of any two or more of theseapproaches may be performed to maintain the channel openings. Forexample, the channel walls may be treated with a bioactive agent whichinhibits tissue growth. The bioactive agent may be delivered locally orsystematically. Also, the channels may be treated with rf energy, heat,electrical energy, or radiation to inhibit tissue overgrowth. Thesetreatments may be performed once, periodically, or in response to theseverity of the channel blockage. For example, the tissue blockage maybe periodically removed with a laser or another tissue-removal tool.Also, mechanical devices and instruments may be deployed in the channelto prevent tissue growth from blocking the channel. Mechanical devicesinclude without limitation conduits, valves, sponges, etc. Thesemechanical devices may be deployed permanently or temporarily. Ifdeployed temporarily, the devices are preferably left in the channel fora sufficient amount of time such that the channel tissue heals coaxiallyaround the device.

FIGS. 1A-1C are simplified illustrations of various states of a naturalairway and a blood gas interface found at a distal end of those airways.FIG. 1A shows a natural airway 100 which eventually branches to a bloodgas interface 102.

Although not shown, the airway comprises an internal layer of epithelialpseudostratified columnar or cuboidal cells. Mucous secreting gobletcells are also found in this layer and cilia may be present on the freesurface of the epithelial lining of the upper respiratory airways.Supporting the epithelium is a loose fibrous, glandular, vascular laminapropria including mobile fibroblasts. Deep in this connective tissuelayer is supportive cartilage for the bronchi and smooth muscle for thebronchi and bronchioles.

FIG. 1B illustrates an airway 100 and blood gas interface 102 in anindividual having COPD. The obstructions 104 impair the passage of gasbetween the airways 100 and the interface 102. FIG. 1C illustrates aportion of an emphysematous lung where the blood gas interface 102expands due to the loss of the interface walls 106 which havedeteriorated due to a bio-chemical breakdown of the walls 106. Alsodepicted is a constriction 108 of the airway 100. It is generallyunderstood that there is usually a combination of the phenomena depictedin FIGS. 1A-1C. Often, the states of the lung depicted in FIGS. 1B and1C may be found in the same lung.

FIG. 1D illustrates airflow in a lung 118 when conduits 200 are placedin collateral channels 112. As shown, collateral channels 112 (locatedin an airway wall) place lung tissue 116 in fluid communication withairways 100 allowing air to pass directly out of the airways 100 whereasconstricted airways 108 may ordinarily prevent air from exiting the lungtissue 116. While the invention is not limited to the number ofcollateral channels which may be created, it is to be understood that 1or 2 channels may be placed per lobe of the lung and perhaps, 2-12channels per individual patient. However, as stated above, the inventionincludes the creation of any number of collateral channels in the lung.This number may vary on a case by case basis. For instance, in somecases in an emphysematous lung, it may be desirable to place 3 or morecollateral channels in one or more lobes of the lung.

Although FIG. 1D depicts a mechanical approach to maintaining channelsin the airway walls, the channel openings may be,maintained using avariety of approaches or combinations of approaches.

As shown in FIGS. 2A-2G, the conduits described herein generally includea center section 208 and at least one extension member (or finger) 202extending from each end of the center section. The extension members, aswill be discussed in more detail below, are capable of deflecting oroutwardly bending to secure the conduit in an opening created in anairway wall thereby maintaining the patency of the opening. Theextension members may deflect such that opposing extension members mayform a V, U or other type of shape when viewed from the side.

Additionally, the conduits shown in FIGS. 2A-2G include a center-controlsegment 235, 256 which restricts or limits radial expansion of thecenter section. The center-control segments are adapted to straighten asthe center section is radially expanded. Once the center-controlsegments become straight or nearly straight, radial expansion of theconduit is prevented. In this manner, the radial expansion of theconduit may be self controlled.

It is understood that the conduits discussed herein are not limited tothose shown in the figures. Instead, conduits of various configurationsmay be used as described herein. Such conduits are described in thefollowing patent applications Ser. No. 09/908,177 filed Jul. 18, 2001;PCT/US03/12323 filed Apr. 21, 2003; Ser. No. 09/947,144 filed Sep. 4,2001; Ser. No. 10/235,240 filed Sep. 4, 2002; and Ser. No. 10/458,085filed Jun. 9, 2003 the entirety of each of which is hereby incorporatedby reference.

Conduit States

The conduits described herein may have various states (configurations orprofiles) including but not limited to (1.) an undeployed state and (2.)a deployed state.

The undeployed state is the configuration of the conduit when it is notsecured in an opening in an airway wall and, in particular, when itsextension members (or fingers) are not outwardly deflected to engage theairway wall. FIG. 2A is a side view of a conduit 200 in an undeployedstate. As shown in this figure, extension members 202A, 202B extendstraight from the ends 210, 212 respectively of center section 208. Theextension members shown in this example are parallel. However, theinvention is not so limited and the extension members need not beparallel.

The deployed state is the configuration of the conduit when it issecured in a channel created in an airway wall and, in particular, whenits extension members are outwardly bent to engage the airway wall suchthat the conduit is fixed in the opening. An example of a conduit in itsdeployed configuration is shown in FIGS. 2B and 2C. FIG. 2B is a sideview of a conduit in its deployed state and FIG. 2C shows a front viewof the conduit of FIG. 2B.

Center Section of the Conduit

As shown in FIGS. 2A-2D, the conduit includes a center section 208having a short passageway. This center section may be a tubular-shapedopen-frame (or mesh) structure having a plurality of ribs. Also, asexplained in more detail below, the center section may be a sheet ofmaterial.

The axial length of the center section or passageway may be relativelyshort. In FIGS. 2A-2D, the passageway's length is about equal to thewidth of a wire segment or rib. Here, the center section serves as abridge or junction for the extension members and it is not required tobe long. The axial length of the passageway may therefore be less than 1mm and even approach 0 mm. In one example, the length of the centersection is less than twice the square root of a cross sectional area ofthe center section. However, the center section may also havepassageways which have lengths greater than 1 mm.

The overall length (L) of the conduit may be distinguished from thelength of the center section because the overall length includes thelengths of the extension members. Further, the overall length (L) isdependent on which state the conduit is in. The overall length of theconduit will typically be shorter when it is in a deployed state asshown in FIG. 2B than when it is in an undeployed state as shown in FIG.2A. The overall length (L) for a deployed conduit may be less than 6 mmand perhaps, between 1 and 20 mm.

FIG. 2C shows a front view of the conduit 200 shown in FIG. 2B. FIG. 2Cshows the passageway having a hexagonal (or circular) cross section. Thecross-section, however, is not so limited. The cross section may becircular, oval, rectangular, elliptical, or any other multi-faceted orcurved shape. The inner diameter (D₁) of the center section, whendeployed, may range from 1 to 10 mm and perhaps, from 2 to 5 mm.Moreover, in some variations, the cross-sectional area of thepassageway, when deployed, may be between 0.2 mm² to 300 mm² and perhapsbetween 3 mm² and 20 mm².

The diameter of the center section, when deployed, thus may besignificantly larger than the passageway's axial length (e.g., a 3 mmdiameter and an axial length of less than 1 mm). This ratio of thecenter section length to diameter (D1) may range from about 0:10 to10:1, 0.1:6 to 2:1 and perhaps from 1:2 to 1:1.

The diameter of the center section, when deployed, may also be nearlyequal to the overall length (L) of the conduit 200. This overall length(L) to diameter (D1) ratio may range from 1:10 to 10:1, 1:6 to 2:1, andperhaps from 1:4 to 1:1. However, the invention is not limited to anyparticular dimensions or ratio unless so indicated in the appendedclaims. Rather, the conduit should have a center section such that itcan maintain the patency of a collateral channel in an airway wall. Thedimensions of the center section (and the conduit as a whole) may bechosen based on the tissue dimensions. When the channel is long in itsaxial length, for example, the length of the center section may likewisebe long or identical to the channel's length.

Extension Members of the Conduit

As mentioned above, extending from the ends of the center section 208are extension members 202A, 202B which, when the conduit is deployed,form angles A1, A2 with a central axis of the passageway. When viewedfrom the side such as in FIG. 2B, opposing extension members may have aV, U, or other shape. The extension members 202A, 202B may thusoutwardly rotate until they sandwich tissue (not shown) between opposingextension members.

The angles A1, A2 may vary and may range from, for example, 30 to 150degrees, 45 to 135 degrees and perhaps from 30 to 90 degrees. Opposingextension members may thus form angles A1 and A2 of less than 90 degreeswhen the conduit is deployed in a channel. For example, angles A1 and A2may range from 30 to 60 degrees when the conduit is deployed.

The conduits of the present invention are effective and may maintain asurgically created opening despite not substantially sandwiching tissuebetween opposing extension members as described above. Additionally, itis not necessary for the conduits of the present invention to preventair from flowing along the exterior of the conduit. That is, air maymove into (and through) spaces between the exterior of the conduit andthe interior wall of the tissue channel. Thus, fluidly sealing the edgesof the conduit to prevent side flow or leakage around the conduit is notcrucial for the conduits to be effective. However, the conduits of thepresent invention are not so limited and may reduce or eliminate sideflow by, for example, increasing the angles A1 and A2 and adding sealantaround the exterior of the conduit.

Moreover, the angle A1 may be different than angle A2. Accordingly, theconduit may include proximal extension members which are parallel (ornot parallel) to the distal extension members. Additionally, the anglecorresponding to each proximal extension member may be different oridentical to that of another proximal extension member. Likewise, theangle corresponding to each distal extension member may be different oridentical to that of another distal extension member.

The extension members may have a length between 1 and 20 mm and perhaps,between 2 and 6 mm. Also, with reference to FIG. 2C, the outer diameter(D₂) of a circle formed by the free ends of the extension members mayrange from 2 to 20 and perhaps, 3 to 10 mm. However, the invention isnot limited to the dimensions disclosed above. Furthermore, the lengthof the distal extension members may be different than the length of theproximal extension members. The length of the distal extension membersmay be, for example, longer than that of the proximal extension members.Also, the lengths of each proximal extension member may be different oridentical to that of the other proximal extension members. Likewise, thelengths of each distal extension member may be different or identical tothat of the other distal extension members.

The number of extension members on each end of the center section mayalso vary. The number of extension members on each end may range from2-10 and perhaps, 3-6. Also, the number of proximal extension membersmay differ from the number of distal extension members for a particularconduit. Moreover, the extension members may be symmetrical ornon-symmetrical about the center section. The proximal and distalextension members may also be arranged in an in-line pattern or analternating pattern. The extension members or the center section mayalso contain barbs or other similar configurations to increase adhesionbetween the conduit and the tissue. The extension members may also haveopenings to permit tissue ingrowth for improved retention.

The shape of the extension members may also vary. They may beopen-framed and somewhat petal-shaped as shown in FIGS. 2A-2D. In thesefigures, the extension members 202A, 202B comprise wire segments or ribsthat define openings or spaces between the members. However, theinvention is not so limited and the extension members may have othershapes. The extension members may, for example, be solid or they may befilled.

In another variation the conduit is constructed to have a deliverystate. The delivery state is the configuration of the conduit when it isbeing delivered through a working channel of a bronchoscope, endoscope,airway or other delivery tool. The maximum outer diameter of the conduitin its delivery state must therefore be such that it may fit within thedelivery tool, instrument, or airway.

In one variation, the conduit is radially expandable such that it may bedelivered in a smaller working channel of a scope while maximizing thediameter to which the conduit may expand upon deployment. For example,sizing a conduit for insertion into a bronchoscope having a 2 mm orlarger working channel may be desirable. Upon deployment, the conduitmay be expanded to have an increased internal diameter (e.g., 3 mm.)However, the invention is not limited to such dimensions. It iscontemplated that the conduits 200 may have center sections that areexpanded into a larger profile from a reduced profile, or, the centersections may be restrained in a reduced profile, and upon release of therestraint, return to an expanded profile.

Additionally, the conduit need not have a smaller delivery state. Invariations where the center section is not able to assume a secondsmaller delivery profile, a maximum diameter of the first or deployedprofile will be sufficiently small such that the conduit may be placedand advanced within an airway or a working channel of a bronchoscope orendoscope. Also, in cases where the conduit is self-expanding, thedeployed shape may be identical to the shape of the conduit when theconduit is at rest or when it is completely unrestrained.

Additionally the conduit may be partially expanded in its proximalregion in the delivery state, as shown in figure X. The partiallyexpanded portion would still me sized small enough to fit within theworking channel of the bronchoscope, but would be significantly larger(e.g., 0.5-2 mm) larger that the distal portion of the conduit. Thispartial expansion allows for easy placement of the conduit by providinga physical stop for the conduit within the airway wall. After theconduit is placed the entire conduit can be expanded to its intendedexpanded shape.

The partial expansion state can also be achieved by partially inflatingthe proximal section of the conduit with a separate balloon on thedelivery device. Another possible method is to design the conduit topreferentially expand the proximal section before the distal section,thereby partially expanding the conduit to create the size differential,placing the stent inside the airway wall with the aid of the stop, andthen fully expanding the conduit.

Control Members

The conduit 200 shown in FIGS. 2A-2D also includes diametric-controlsegments, tethers, or leashes 235 to control and limit the expansion ofthe center section 208 when deployed. This center-control segment 235typically is shaped such that when the conduit radially expands, thecenter-control segment bends until it is substantially straight or nolonger slack. Such a center-control segment 235 may be circular orannular shaped. However, its shape may vary widely and it may have, forexample, an arcuate, semi-circular, V, or other type of shape whichlimits the expansion of the conduit.

Typically, one end of the center-control segment is attached or joinedto the center section at one location (e.g., a first rib) and the otherend of the center-control segment is connected to the center section ata second location (e.g., a rib adjacent or opposite to the first rib).However, the center-control segments may have other constructs. Forexample, the center-control segments may connect adjacent ornon-adjacent center section members. Further, each center-controlsegment may connect one or more ribs together. The center-controlsegments may further be doubled up or reinforced with ancillary controlsegments to provide added control over the expansion of the centersection. The ancillary control segments may be different or identical tothe primary control segments.

FIG. 2B illustrates the conduit 200 in its deployed configuration. Asdiscussed above, the center-control segments 235 may bend or otherwisedeform until they maximize their length (i.e., become substantiallystraight) such as the center-control segments 235 shown in FIG. 2B.However, as discussed above, the invention is not so limited and othertypes of center-control segments may be employed.

As shown in FIGS. 2E-2G, control segments 252 may also be used to joinand limit the expansion of the extension members 254 or the controlsegments may be placed elsewhere on the conduit to limit movement ofcertain features to a maximum dimension. By controlling the length ofthe control segments, the shape of the deployed conduit may becontrolled. In the conduit shown in FIGS. 2E-2G, the conduit includesboth center-control segments 256 and distal control segments 252. Thecenter-control segments are arcuate shaped and join adjacent ribsections of the center section and the distal-control segments arearcuate and join adjacent distal extension members.

FIG. 2F illustrates the conduit in a deployed configuration and showsthe various control members straightening as the extension members andcenter section deploy. The proximal extension members, however, are notrestricted by a control member and consequently may be deflected to agreater degree than the distal extension members. Accordingly, a conduithaving control members connecting, for example, regions of the centersection and having additional control segments connecting extensionmembers, may precisely limit the maximum profile of a conduit when it isdeployed. This is desirable where overexpansion of the conduit ishazardous.

This also serves to control the deployed shape of the conduit by, forinstance, forcing angle A1 to differ from angle A2. Using controlsegments in this manner can provide for cone-shaped conduits if thevarious types of control-segments have different lengths. For example,providing longer proximal-control segments than distal-control segmentscan make angle A1 larger than angle A2. Additionally, cylindrical-shapedconduits may be provided if the center-control segments and theextension-control segments are sized similarly such that angle A1 equalsangle A2. Again, the control segments straighten as the conduit expandsand the conduit is thus prevented from expanding past a predeterminedamount.

The control segments, as with other components of the conduit, may beadded or mounted to the center section or alternatively, they may beintegral with the center section. That is, the control segments may bepart of the conduit rather than separately joined to the conduit withadhesives or welding, for example. The control segments may also bemounted exteriorly or interiorly to the members to be linked.Additionally, sections of the conduit may be removed to allow areas ofthe conduit to deform more readily. These weakened areas provide anotherapproach to control the final shape of the deployed conduit. Details forcreating and utilizing weakened sections to control the final shape ofthe deployed conduit may be found in U.S. Pat. No. 09/947,144 filed onSep. 4, 2001.

Manufacture and Materials

The conduit described herein may be manufactured by a variety ofmanufacturing processes including but not limited to laser cutting,chemical etching, punching, stamping, etc. For example, the conduit maybe formed from a tube that is slit to form extension members and acenter section between the members. One variation of the conduit may beconstructed from a metal tube, such as stainless steel, 316L stainlesssteel, titanium, titanium alloy, nitinol, MP35N (anickel-cobalt-chromium-molybdenum alloy), etc. Also, the conduit may beformed from a rigid or elastomeric material that is formable into theconfigurations described herein. Also, the conduit may be formed from acylinder with the passageway being formed through the conduit. Theconduit may also be formed from a sheet of material in which a specificpattern is cut. The cut sheet may then be rolled and formed into a tube.The materials used for the conduit can be those described above as wellas a polymeric material, a biostable or implantable material, a materialwith rigid properties, a material with elastomeric properties, or acombination thereof. If the conduit is a polymeric elastic tube (e.g. athermoplastic elastomer), the conduit may be extruded and cut to size,injection molded, or otherwise formed.

Additionally, the conduits described herein may be comprised of a shapememory alloy, a super-elastic alloy (e.g., a NiTi alloy), a shape memorypolymer, or a shape memory composite material. The conduit may beconstructed to have a natural self-assuming deployed configuration, butis restrained in a pre-deployed configuration. As such, removal of therestraints (e.g., a sheath) causes the conduit to assume the deployedconfiguration. A conduit of this type could be, but is not limited tobeing, comprised from an elastic polymeric material, or shape memorymaterial such as a shape memory alloy. It is also contemplated that theconduit could comprise a shape memory alloy such that, upon reaching aparticular temperature (e.g., 98.5° F.), it assumes a deployedconfiguration.

Also, the conduit described herein may be formed of a plasticallydeformable material such that the conduit is expanded and plasticallydeforms into a deployed configuration. The conduit may be expanded intoits expanded state by a variety of devices such as, for example, aballoon catheter.

The conduit's surface may be modified to affect tissue growth oradhesion. For example, an implant may comprise a smooth surface finishin the range of 0.1 micrometer to 0.01 micrometer. Such a finish mayserve to prevent the conduit from being ejected or occluded by tissueovergrowth. On the other hand, the surface may be roughened or porous.The conduit may also comprise various coatings and tissue barriers asdiscussed below.

Tissure Barrier

FIG. 3A illustrates another variation of a conduit 200 having a tissuebarrier 240. The tissue barrier 240 prevents tissue ingrowth fromoccluding the collateral channel or passage of the conduit 200. Thetissue barrier 240 may coaxially cover the center section from one endto the other or it may only cover one or more regions of the conduit200. The tissue barrier may completely or partially cover the conduit solong as the ends are at least partially open. Moreover, the tissuebarrier may only be placed on the center section of the conduit. Thetissue barrier 240 may be located about an exterior of the conduit'ssurface, about an interior of the conduit's surface, or the tissuebarrier 240 may be located within openings in the wall of the conduit'ssurface. Furthermore, in some variations of the invention, the centersection 208 itself may provide an effective barrier to tissue ingrowth.The tissue barrier, of course, should not cover or block the entranceand exit of the passageway such that air is prevented from passingthrough the conduit's passageway. However, in some constructs, thetissue barrier may partially block the entrance or exit of thepassageway so long as air may continue to pass through the conduit'spassageway.

The tissue barrier may be formed from a material, mesh, sleeve, orcoating that is a polymer or an elastomer such as, for example,silicone, fluorosilicone, polyurethane, PET, PTFE, or expanded PTFE.Other biocompatible materials will work, such as a thin foil of metal,etc. The coatings may be applied, for example, by either dip coating,molding, spin-coating, transfer molding or liquid injection molding.Alternatively, the tissue barrier may be a tube of a material and thetube is placed either over and/or within the conduit. The tissue barriermay then be bonded, crimped, heated, melted, shrink fitted or fused tothe conduit. The tissue barrier may also be tied to the conduit with afilament of, for example, a suture material.

Still other techniques for attaching the tissue barrier include: solventswelling applications and extrusion processes; wrapping a sheet ofmaterial about the conduit, or placing a tube of the material about theconduit and securing the tube to the conduit. The tissue barrier may besecured on the interior of the conduit by positioning a sheet or tube ofmaterial on the inside of the center section and securing the materialtherein.

The tissue barrier may also be formed of a fine mesh with a porosity ortreatment such that tissue may not penetrate the pores. For example, aChronoFlex™ DACRON® or TEFLON® mesh having a pore size of 100-300microns may be saturated with collagen or another biocompatiblesubstance. This construct may form a suitable tissue barrier. The meshmay be coaxially attached to a frame such as the open frame structuresdisclosed above. Still other suitable frames include a continuous spiralmetallic or polymeric element. Given the mesh's radial strength or lackthereof, the use of a reinforcement element serves to prevent theimplant from collapsing. Also, as described below, other substances maybe applied to the exterior surface of the conduit to control elution ofvarious medicines.

FIGS. 3B and 3C respectively illustrate a side view and a front view ofanother conduit 300 having a partial tissue barrier coating. The conduit300 includes a center section 310, a plurality of extension members 320,and a partial tissue barrier 330. The conduit 300 is thus different thanthat shown in FIG. 3A in that the center section is longer and that thetissue barrier 330 only partially covers the extension members 320. Inparticular, the center section 310 shown in FIGS. 3B-3C is cylindricalor tubular-shaped. This shape may be advantageous when a relatively longpassageway is desired. Also, it is to be understood that the overall (orthree dimensional) shape of the center section, when deployed, is notlimited to the shape shown here. Rather, it may have various shapes suchas, for example, rectangular, tubular, conical, hour-glass,hemi-toroidal, etc.

Additionally, the tissue barrier 330 covers only a first region 350 ofthe extension members and leaves a second region 340 of the extensionmembers uncovered. The second or free region 340 of the extensionmembers 320 is shown as being open-framed. However, the invention is notso limited. The second region of the extension members may be solid andit may include indentations, grooves, and recesses for tissue ingrowth.Also, the extension members may include small holes for tissue ingrowth.For example, the second region of the extension members may have a densearray of small holes. In any event, the conduits described herein mayinclude at least one region or surface which is susceptible to tissueingrowth or is otherwise adherent to the tissue. Accordingly, tissueingrowth at the second region 340 of the extension members isfacilitated while tissue growth into the passageway 325 is thwarted.

As shown in FIG. 3D, tissue growth 360 into the uncovered region 340further secures the extension members to the tissue wall 370. Freeregion 340 of the extension members may also include tissue growthsubstances such as epithelial growth factors or agents to encouragetissue ingrowth. Accordingly, conduit 300 may be configured to engagethe tissue wall 370 as well as to allow tissue to grow intopredetermined regions of the conduit.

Visualization Feature

The conduit shown in FIG. 3A also includes a visualization ring ormarker 242. The marker 242 is visually apparent during a procedure. Themarker is observed as the conduit is placed in a collateral channel and,when the marker is even with the opening of the channel, the conduit maybe deployed. In this manner, the visualization feature facilitatesalignment and deployment of the conduits into collateral channels.

The visualization ring or mark may be a biocompatible polymer and have acolor such as white. Also, the visualization feature may protrude fromthe center section or it may be an indentation(s). The visualizationmark may also be a ring, groove or any other physical feature on theconduit. Moreover, the visualization feature may be continuous orcomprise discrete segments (e.g., dots or line segments).

The visualization feature may be made using a number of techniques. Inone example, the mark is a ring formed of silicone and is white. Thepolymeric ring may be spun onto the tissue barrier. For example, a clearsilicone barrier may be coated onto the conduit such that it coaxiallycovers the extension members and the center section as shown in FIG. 3A.Next, a thin ring of white material such as a metal oxide suspended inclear silicone may be spun onto the silicone coating. Finally, anothercoating of clear silicone may be applied to coat the white layer. Theconduit thus may include upwards of 1-3 layers including a tissuebarrier, a visualization mark layer, and a clear outer covering.

The shape of the visualization mark is not limited to a thin ring. Thevisualization mark may be large, for example, and cover an entire halfof the conduit as shown in FIG. 3B. The visualization mark may, forexample, be a white coating disposed on the proximal or distal half ofthe conduit. The visualization mark thus may extend from an end of theextension members to the center section of the conduit. As explained inmore detail below, when such a device is deposited into a channelcreated in lung tissue, the physician may observe when one-half of theconduit extends into the channel. This allows the physician to properlyactuate or deploy the conduit to secure the conduit in the tissue wall.

Accordingly, the visualization member is made visually apparent for usewith, for example, an endoscope. The visualization feature, however, mayalso be made of other vision-enhancing materials such as radio-opaquemetals used in x-ray detection. It is also contemplated that otherelements of the conduit can include visualization features such as butnot limited to the extension members, tissue barrier, control segments,etc.

In some variations of the invention, it was found that incorporation ofa bioactive, as discussed herein, or other substance into the coatingcaused a coloration effect in the composition layer (e.g., the polymerturns white). This coloration obscures the support member structure inthe layer making it difficult to identify the edges and center of thesupport member or implant. As discussed herein, placement of the implantmay depend upon positioning the center of the implant within the openingin tissue. If the support member structure is identifiable, then one isable to visually identify the center of the implant. When thecomposition colors obscures the support member or renders the implantotherwise opaque, it may become difficult to properly place the device.This may be especially true when the composition layer extendscontinuously over the support member.

Additionally, the coloration may render the visualization mark difficultto identify especially under direct visualization (e.g., using a scope)In some cases it was undesirable to simply add additional substances onor in the composition layer for marking because such substances couldpossibly interfere with the implant's ability to deliver the substanceas desired. To address these issues, a variation of the inventionincludes a delivery device for delivering an expandable implant (such asthose described herein and in the cases referenced herein), where thedelivery device includes an expandable member having an expandableimplant located about the expandable member. Where the implant and theexpandable member are of different visually identifiable colors orshades such that they distinction is easy to identify under endoscopicor bronchoscopic viewing.

In one example, as shown in FIG. 9C, a balloon catheter has a coloredsleeve 306 located about the balloon. The sleeve 306 comprises avisually identifiable color where selection of the colors should easeidentification of the implant an endoscopic visualization system (e.g.,blue or a similar color that is not naturally occurring within thebody.) The implant is placed about the sleeve 306 where the proximal anddistal areas of the implant would be identifiable by the difference incolor. Such a system allows a medical practitioner to place the implant200 properly by using the boundary of the implant 200 to guide placementin the tissue wall. The sleeve 306 may be fashioned from any expandablematerial, such as a polymer. Optionally, the sleeve 306 may also providean elastic force to return the balloon to a reduced profile afterexpansion of the balloon. Such a system allows for identificationwithout affecting the properties of the implant.

It should be noted that variations of the invention include coloring theballoon itself, or other expandable member, a color that meets the abovecriteria.

In another variation, the visualization mark may comprise providing acontrast between the implant and a delivery catheter. In one example theimplant is appears mostly white and while mounted on a contrasting colorinflation balloon. In this example the implant would be placed over ablue deflated balloon catheter. The proximal and distal areas of theimplant would be flanked by the deflated blue balloon, thus giving theappearance of a distinct distal and proximal end of the implant. Thiswould allow a physician to place the implant properly by using the blueflanks as a guide for placing the central white portion in the tissuewall. Similarly, a colored flexible sheath covering the balloon wouldalso suffice.

It is noted that while the visualization features described above aresuitable for use with the implants described herein, the inventivefeatures are not limited as such. The features may be incorporated intoany system where placement of an implant under direct visualizationrequires clear identification of the implant regardless of whether theimplant is opaque or colored.

Bioactive Agents

As discussed above, the bio-active substance or combination of bioactivesubstances is selected to assists in modifying the healing response as aresult of the trauma to the lung tissue resulting from creation of thecollateral channel. As noted above, the term lung tissue is intended toinclude the tissue lining the airway, the tissue beneath the lining, andthe tissue within the lung but exterior to the airway (e.g., lungparenchyma.) The purpose of modifying the healing response is to furtherextend the patency of the channel or implant to increase the durationwhich trapped gasses may exit through the implant into the airways. Theterm antiproliferative agent is intended to include those bioactivesubstances that directly modify the healing response described herein.

The bioactive substances are intended to interact with the tissue of thesurgically created channels and in particular, lung tissue. Thesesubstances may interact with the tissue in a number of ways. They may,for example, 1.) accelerate cell proliferation or wound healing toepithelialize or scar the walls of the surgically-created channel tomaintain its patent shape or 2.) the substances may inhibit or halttissue growth when a channel is surgically created through an airwaywall such that occlusion of the channel due to tissue overgrowth isprevented. Additionally, other bioactive agents may inhibit woundhealing such that the injury site (e.g., the channel or opening) doesnot heal leaving the injury site open and/or inhibit infection (e.g.,reduce bacteria) such that excessive wound healing does not occur whichmay lead to excessive tissue growth at the channel thereby blocking thepassageway.

A variety of bioactive substances may be used alone or in combinationwith the devices described herein. Examples of bioactive substancesinclude, but are not limited to, antimetabolites, antithrobotics,anticoagulants, antiplatelet agents, thorombolytics, antiproliferatives,antinflammatories, agents that inhibit hyperplasia and in particularrestenosis, smooth muscle cell inhibitors, growth factors, growth factorinhibitors, cell adhesion inhibitors, cell adhesion promoters and drugsthat may enhance the formation of healthy neointimal tissue, includingendothelial cell regeneration. The positive action may come frominhibiting particular cells (e.g., smooth muscle cells) or tissueformation (e.g., fibromuscular tissue) while encouraging different cellmigration (e.g., endothelium, epithelium) and tissue formation(neointimal tissue).

Still other bioactive agents include but are not limited to analgesics,anticonvulsives, anti-infectives (e.g., antibiotics, antimicrobials),antineoplastics, H2 antagonists (Histamine 2 antagonists), steroids,non-steroidal anti-inflammatories, hormones, immunomodulators, mast cellstabilizers, nucleoside analogues, respiratory agents,antihypertensives, antihistamines, ACE inhibitors, cell growth factors,nerve growth factors, anti-angiogenic agents or angiogenesis inhibitors(e.g., endostatins or angiostatins), tissue irritants (e.g., a compoundcomprising talc), poisons (e.g., arsenic), cytotoxic agents (e.g., acompound that can cause cell death), various metals (silver, aluminum,zinc, platinum, arsenic, etc.), epithelial growth factors or acombination of any of the agents disclosed herein.

Examples of agents include pyrolitic carbon, titanium-nitride-oxide,taxanes, fibrinogen, collagen, thrombin, phosphorylcholine, heparin,rapamycin, radioactive 188Re and 32P, silver nitrate, dactinomycin,sirolimus, everolimus, Abt-578, tacrolimus, camptothecin, etoposide,vincristine, mitomycin, fluorouracil, or cell adhesion peptides. Taxanesinclude, for example, paclitaxel, 10-deacetyltaxol,7-epi-10-deacetyltaxol, 7-xylosyl-10-deacetyltaxol, 7-epi-taxol,cephalomannine, baccatin III, baccatin V, 10-deacetylbaccatin III,7-epi-10-deacetylbaccatin III, docetaxel.

Of course, bioactive materials having other functions can also besuccessfully delivered in accordance with the present invention. Forexample, an antiproliferative agent such as methotrexate will inhibitover-proliferation of smooth muscle cells and thus inhibit restenosis.The antiproliferative is desirably supplied for this purpose until thetissue has properly healed. Additionally, localized delivery of anantiproliferative agent is also useful for the treatment of a variety ofmalignant conditions characterized by highly vascular growth. In suchcases, an implant such as a implant could be placed in the surgicallycreated channel to provide a means of delivering a relatively high doseof the antiproliferative agent directly to the target area. Avasodilator such as a calcium channel blocker or a nitrate may also bedelivered to the target site. The agent may further be a curative, apre-operative debulker reducing the size of the growth, or a palliativewhich eases the symptoms of the disease. For example, tamoxifen citrate,Taxol® or derivatives thereof Proscar®, Hytrin®, or Eulexin® may beapplied to the target site as described herein.

Variations of the invention may also include fibrinolytics such as tPA,streptokinase, or urokinase, etc. Such fibrinolytics prevent or reducethe accumulation of fibrin within the opening. Accumulation of fibrin inthe opening may result from inflammation of the tissue. The fibrin mayform a structure which makes it easier for tissue to grow into theopening using the fibrin structure as a framework. Use of fibrinolytics,either topically, locally, or on the implant, serves to remove or hinderthe network of fibrin from forming within the opening (or implant) andtherefore aids in modifying the healing response.

In the event that poisonous and toxic compounds are delivered, theyshould be controlled so that inadvertent death of tissue does not occur.The poisonous agent should be delivered locally or only be effectivelocally. One method for delivering the bioactive agent locally is toassociate the bioactive agent with an implant. For example, the implantsdescribed herein may include a bioactive substance or medicine depositedonto the interior, the exterior, or both the interior and exteriorsurfaces of the implant. The bioactive substance may remain on theimplant so that it does not leach. Cells that grow into the surgicallycreated channel contact the poison and die. Alternatively, the bioactiveagent may be configured to gradually elute as discussed below.

When used in the lungs, the implant modifies the healing response of thelung tissue (e.g., at the site of newly created hole/channel) for asufficient time until the healing response of the lung tissue subsidesor reduces such that the hole/channel becomes a persistent air path. Forexample, the implant and bioactive substance will modify the healingresponse for a sufficient time until the healing response is reducedand, from a visual observation, the body treats the opening essentiallyas a natural airway passage rather than as an injury to the airway wall.

In one variation of the invention which modifies the healing response asdescribe above, the implant provides a steady release rate of bio-activesubstance as well as has a sufficient amount of available bio-activesubstance to modify the healing response of the lung tissue. As notedherein, the term lung tissue is intended to include the tissue liningthe airway, the tissue beneath the lining, and the tissue within thelung but exterior to the airway (e.g., lung parenchyma.) Such a deliveryprofile allows for a concentration gradient of drug to build in thesetissues adjacent to the delivery site of the implant.

It is believed that forming the concentration gradient affects thehealing response of the lung tissue so that the implant does not becomeoccluded as a result of the healing response. Because the implant isoften placed in the airway wall it is exposed to the healing process ofthe multiple tissues. Providing a sufficient amount of bio-activesubstance allows for the formation of a concentration of the bio-activesubstance across these various tissues. In one variation of theinvention it is believed that the fluids from these tissues enter intothe composition layer of the device. The fluids then combine with thebio-active substances and migrate out of the composition layer to settleinto the lung tissue. A concentration gradient forms when the drug‘saturates’ local tissue and migrates beyond the saturated tissues.Furthermore, by providing a sufficient delivery rate, the healingresponse may be affected or suppressed during the critical timeimmediately after the wounding caused by creation of the collateralchannel when the healing response is greatest.

To select a proper combination of drug and polymer, it is believed thatthe solubility parameter of the polymer must be matched with thebio-active substance to provide an acceptable slow elution rate from thepolymer. Next, the polymer itself must be selected to have the properattributes, such as a proper diffusion coefficient (to slow fluidentering and departing from the implant), and proper mechanicalexpansion properties (to allow for the significant expansion of thepolymer to accommodate formation of the grommet shape.)

The solubility parameter is defined as the square root of the cohesiveenergy of the molecules in a compound. The level of control that apolymer has over the elution of a drug is the difference between thesolubility parameters of the polymer and the solubility parameter of thedrug. To select a polymer with the approximate diffusion a polymer witha high internal density could be selected to be less permeable to acomplex molecule such as paclitaxel. Using a polymer with high internaldensity also accommodated the significant expansion required of thepolymer to form the structure necessary to grommet about the airwaywall. An example of the polymer selection is found below.

It is also important to note that paclitaxel is a taxane that isregarded as a microtubule stabilizer. The benefits of a microtubulestabilizing substance for use in vascular drug eluting stents isdiscussed, for example, in U.S. Pat. No. 5,616,608 to Kinsella et al.This type of drug operates to enhance microtubule polymerization whichinhibits cell replication by stabilizing microtubules in spindles whichblock cell division. In contrast to the vascular applications, theimplant for use in the present invention may use microtubule stabilizingsubstances such as taxanes (e.g., paclitaxel) as well as thosemicrotubule destabilizing substances that are believed to promotemicrotubule disassembly in preventing cell replication. Suchdestabilizing substances include, but are not limited to vincristine,vinblastine, podophylotoxin, estramustine, noscapine, griseofulvin,dicoumarol, a vinca alkaloid, and a combination thereof.

Additionally, the exterior surface of the implant may be treated viaetching processes or with electrical charge to encourage binding of thebioactive substances to the implant. The exterior surface may also beroughened to enhance binding of the medicine to the surface as discussedin U.S. Patent Application Publication No. 2002/0098278. See also U.S.Patent Application Publication Nos. 2002/0071902, 2002/0127327 and U.S.Pat. No. 5,824,048 which discuss various techniques for coating medicalimplants.

Although the implant may comprise a frame or body with a bioactivematrix disposed or otherwise associated therewith, the invention is notso limited. In one variation, the support member is formed from apolymer and the composition is joined to the polymeric support member.Alternatively, the bioactive substances may be placed directly onto thepolymeric support member.

Various additional substances may be used incorporated into the deviceto reduce an adverse reaction resulting from possible contact with theimplant and the airway wall. Adverse reactions include, but are notlimited to, granulation, swelling, and mucus overproduction. Thesesubstance may may also be inhaled, injected, orally applied, topicallyapplied, or carried by the implant. These substances may includeanti-inflammatory, infection-fighting substances, steroids, mucalytics,enzymes, and wound healing-accelerating substances. Examples of thesesubstances include but are not limited to, acetylcysteine, albuterolsulfate, ipratropium bromide, dornase alfa, and corticosteroids.

As noted above, conventional vascular drug eluting devices are notdesigned for exposure multiple tissue environments. Moreover, thosedevices are placed in an environment where a constant flow of bloodcreates an environment requiring a different delivery mechanism andrate. As noted herein, experiments with conventional coronary drugeluting implants demonstrated that such devices were unsuitable.

Channel Creation Devices and Methods

As discussed above, the use of low temperature devices, (e.g.,mechanical devices, newer generation RF-type devices, etc.) to createthe channel may result in less trauma to surrounding tissue and minimizethe healing response of the tissue. FIGS. 4A-4C illustrates creation ofthe collateral channel and selecting a treatment site in the airway 100.As will be discussed in more detail below, a single device may be usedto select the site and create the channel. Moreover, another variationof the invention includes using such a device to deploy the conduit atthe target site. However, the invention also contemplates using separatedevices to perform each step or a combination of steps.

As shown in FIG. 4A, a device 602 is advanced, for example, via abronchoscope 404, into the airway 100. A potential treatment site isthen inspected to determine whether or not a blood vessel is inproximity to the site. Naturally, if a blood vessel is detected, thesurgeon has the option of selecting a different site. The device 602 maybe a Doppler ultrasound device, a thermal device, an imaging device,etc.

FIG. 4B illustrates another variation of selecting a site for a channel.In this variation, a piercing member (e.g., a blade affixed to a shaft,a needle, cannula, sharpened tube or rod, etc.,) 604 is advanced intothe airway wall. Once the piercing member 604 is inserted into theairway wall, the surgeon may inspect the area for blood to determinewhether the device punctured a blood vessel. After the opening iscreated the surgeon may also remove collect a biopsy of material behindthe airway wall. If the opening is large enough as created by a balloon,as described herein, the surgeon may use forceps to visually obtain thesample. This may preferable to a blind method of obtaining biopsies,considering that the risk of bleeding may be reduced because the areahas been scanned for blood vessels.

The piercing member 604 may have a lumen and may be open at a distal endor closed. In those cases where the piercing member 604 is hollow andhas an opening at or near the distal end, the surgeon may aspirate thesite using the piercing member 604 to determine whether a blood vesselis present and/or penetrated. For example, flashback catheters containchambers which will fill with blood upon the penetration of a vessel bythe distal tip of the catheter. The piercing member may be incorporatedto have a flashback chamber to detect the presence of blood flow from apenetrated vessel. Using these approaches, a target site may not beselected until after a hole is made in the airway 100 wall. It should benoted that a piercing member may be of a diameter which results inclosure of the puncture site upon removal of the piercing member.Alternatively, the piercing member may be of a sufficient size orconstruction that the hole remains open upon removal of the piercingmember. In any case, the piercing member or another device may be usedto mark the site of the opening (e.g., via ink, dye, physical marker,via application of electrical energy, etc.) Furthermore, the inventionincludes use of both a detecting device as described above incombination with a piercing member. For example, the site may beinspected by the detecting device prior to insertion of a piercingmember.

The piercing member lumen may also used to deliver therapeutic fluids tothe lungs. For example, in case of bleeding after channel creation thephysician may apply epinephrine or saline the lungs. Alternatively thephysician may use the piercing member to apply epinephrine to the airwaywall prior to creation of the channel, to prevent bleeding. This may bedone by injecting directly into the airway wall at or about the site ofpassage creation; singly or in a surrounding pattern of multipleapplications. The physician may also use the piercing member lumen toapply any of the bioactive agents discussed herein, before or afterpassage creation.

Because it may be desirable to reach remote airways within the lung, itmay be necessary to fully articulate the scope 404 to access and inspecta desirable site. Therefore, to inspect the site and create an opening,it may be desirable to maintain the scope 404 in a fixed position andsimply advance/retract various components of the scope or devices in thescope. Accordingly, a piercing member may be selected to have a lengththat will sufficiently pass through the airway wall, while being smallenough that it will also pass through a fully articulated bronchoscope.Furthermore, the piercing member may have sections of varying stiffnesswhere a distal portion, (that is sufficient stiff to penetrate thetissue) may be of a length such that it is able to advance through afully articulated bronchoscope. For example, the piercing member maycomprised of a sharpened cannula which has a length from between 2 mm to30 mm. The diameter may range between 16 Ga to 25 Ga or larger. Thecannula may be affixed to a catheter having a relatively flexibleproximal portion. In any case, the length of the piecing member 604 mayvary as needed.

The piercing member is not limited to a cannula, it may be of solidconstruction, such as a sharpened rod or wire. Additionally the piercingmember may be adapted with an elongate member, such as a wire, rod, ortube, which extends throughout the device. The purpose of the elongatemember is to provide column strength to the piercing member andnecessary bending resistance to the catheter, because it has been foundthat the device must have high column strength to effectively pierce theairway wall, otherwise the device will deflect and not create apassageway. The elongate member may be utilized to expose and retractthe piercing member within the catheter, as the elongate member mayextend throughout the device to a user interface. The elongate memberand piercing member may also be constructed from one piece of material,thereby making them one part. Alternatively the elongate member may be aseparate part welded, bonded, mechanically attached, or a combinationthereof, to the piercing member.

However, it is understood, that the current invention is not limited toany particular length of the piercing member. Furthermore, the piercingmember may be comprised of a resilient polymer, a polymer with areinforced structure (e.g., a braid, coil, etc.), a super-elastic alloy,a metallic material with sufficient resilience, etc, such that it maynavigate through a fully articulated bronchoscope yet return to itsoriginal profile upon exiting the working channel of the scope.

In some variations of the invention, the piercing member of the devicemay be retractable within a lumen of an elongate shaft so as to preventdamage to the bronchoscope or to tissue as the device advances to thetarget site. Additionally the piercing member may be retracted after theinitial piercing of the airway wall, and blunt trauma may be used tofurther push the remaining portion of the catheter into the airway wall.This technique may help avoid additional bleeding and pneumothoraxesfrom an exposed piercing member. The catheter may be advanced totortuous locations, therefore the device may incorporate low frictionmaterials to make it easier to reach the treatment site. The materialsmay be selected from a group of low friction polymers, for example PTFE.Low friction materials may also be applied as a coating onto the piercedmember or elongate member, for example PTFE or titanium nitride.Reducing the contact surface area between the members may also help toreduce friction. Adding or removing material from the surfaces ofmembers is one way to reduce contact surface area. For example attachinga closed coiled spring around the piercing member or elongate member,effectively reduces the surface area contacted between the elongatemember and lumen because only the peaks of the coils contact the lumen.

In additional variations of the invention, as shown in FIG. 4C, aballoon catheter may be configured with a piercing member 604. In thisvariation the balloon 614 advances into the opening created by thepiercing member (in which case the piercing member either retracts intothe catheter or advances with the catheter.) The balloon 614 would thendeploy to dilate the opening for ease of later inserting a conduit.Alternatively, a conduit may be located on the balloon itself anddeployed on inflation of the balloon. Examples of variations of such aballoon catheter may be found below. Furthermore, the needle may beaffixed to a tapered introducer type device which is able to dilate theopening.

The piercing member 604 may also be used to deliver bioactive substances(as described herein) to the site of the opening. In such a case, thepiercing member 604 may deliver the bioactive substance during creationof the opening (e.g., see FIG. 4B) or after dilation of the opening (seee.g., FIG. 4C). In another variation of the invention, the piercingmember 604 may be have a multi-lumen cross-section with different lumensbeing reserved, for example, for inflating the balloon, aspirating thesite for blood, drug delivery, and suction of mucous/fluids at the site.In any of the variations described herein, an obturator (not shown) maybe used to fill a lumen during advancement of the piercing member intotissue so that the lumen does not become blocked with tissue or otherdebris. The obturator may be a guide-wire, polymeric column of material,etc.

FIG. 4D illustrates a variation of a balloon catheter 606 having apiercing member 604. In this variation, the balloon catheter 606comprises two lumens 608, 610. One lumen 608 is fluidly coupled to theinterior of the balloon 614 while the second lumen 610 extends throughthe piercing member 604. It is understood that the device 606 may beconfigured to have any number of lumens as required. As discussed above,the piercing member 604 may either be fixedly attached to the distal endof the balloon catheter 606. Alternatively, the piercing member 604 maybe retractable into the balloon catheter 606 so that it does not causedamage to lung parenchyma when the catheter 606 is inserted into theairway 100 wall. As illustrated, the balloon catheter 606 may have atapered section 612 between the piercing member 604 and the balloon 614to assist in insertion of the balloon 614 into the opening 112.

FIG. 4E illustrates an additional variation of a piercing member 604according the present invention. As illustrated, the piercing member 604may have a number of ports 616 (e.g., openings, holes, etc.). The ports616 may allow for either aspiration of blood or delivery of bio-activesubstances as described herein. Furthermore, although the piercingmembers 604 shown herein are configured with a beveled tip, it iscontemplated that the tip may be any type of tip sufficient to penetratethe airway wall. For instance, the tip may be non-beveled with sharpenededges, the tip may be a trocar tipped needle, or any other availableneedle tip configuration. The piercing member 604 of FIG. 4E is alsoshown with an obturator placed therein. In this configuration, theobturator 618 blocks the lumen of the piercing member 604 at the distalend. Moreover, as shown, a portion of the obturator 618 may be sizedsuch that it is smaller than a lumen of the piercing member 604 to allowfor delivery of substances or aspiration through the ports 616.

FIG. 4F illustrates yet another variation of a balloon catheter 606having a piercing member 604. In this variation, as indicated by thearrow, the piercing member 604 is capable of being retracted into thecatheter 606. The ability to retract the piercing member 604 into thecatheter 606 reduces the possibility of the piercing member 604 causingdamage to any lung tissue that is behind the airway wall. Clearly, thisvariation combines the channel-making step with the conduit deploymentstep. Also, as shown in the figure, the catheter 606 may have a conduit202 placed over the balloon 614. Such a variation may create the openingor channel and then deploy the conduit 200 with a single device.

FIG. 4G illustrates another variation of a balloon catheter 606 wherethe piercing member 604 is slidably located within the catheter 606. Inthis variation, the catheter 606 contains an outer and inner sheaths620, 622 which define two lumens. The lumen defined by the inner sheath622 extends to the distal end of the catheter 606 and may be used todeliver bioactive substances, for suction, or for irrigation.

It is also contemplated that variations of the invention include apiercing member which is affixed to the catheter. Alternatively, thepiercing member could have a flexible body that extends through thecatheter to a proximal hub which is able to be coupled to a vacuumsource, a source of medication, etc. Furthermore, either the piercingmember and/or balloon catheter may be “pre-loaded” with a bioactivesubstance. Such a feature allows improves the precision of amount ofsubstance delivered to the desired site.

As mentioned above, the piercing member 604 may be of a sufficient sizeor construction that the hole remains open upon removal of the piercingmember. Once variation of this as shown in FIG. 4H, where the device hasa conical tip 658 with a lumen extending through out. A piercing member604 is extendable past the distal tip to pierce the airway wall, afterthe initial opening is made, the rest of the device can be driven intothe airway wall, gradually expanding the hole to a desirable diameterwhich allows the conduit to be subsequently placed.

The makeup of airway tissue may require a considerable amount of forceto create a channel with the piercing device. Therefore, it willgenerally be easier to create a channel if the device has sufficientcolumn strength to avoid bending of the device when applying a force atthe proximal end of the device.

Additional variations of the invention may incorporate a nondistensibleballoon to overcome the toughness of the airway tissue. Nondistensibleballoons are generally made up of relatively inelastic materialsconsisting of PET, nylons, polyurethanes, polyolefins, PVC, and othercrosslinked polymers. The makeup of airway tissue may be very tough andresist radial expansions. Therefore it will be generally easier toexpand the channel in the airway wall using high pressure nondistensibleballoons (>6 atm), which generally inflate in a uniform shape.

Nondistensible balloons will occupy a greater mass than distensibleballoons because they in an inelastic predetermined form. Too muchballoon mass will have too large of a working diameter, which in turnwill hinder entry into a channel. Working diameter is the smallesteffective diameter opening the uninflated nondistensible balloon can beinserted into. Therefore it is desirable to have the uninflatednondistensible balloon to have a working diameter close to the diameterof the piercing device 604. This can be attained by using a thin walledballoon, using a balloon with a small distal profile, by using a balloonwith a distal end which is close in actual diameter to the diameter ofthe piercing member or by using a balloon which folds into a low profilestate, or a combination of these.

As shown in FIG. 4I, a device of insufficient sharpness will “tent” theairway wall 450. Tenting occurs when a device is placed against anairway wall with significant force but with no puncturing of the airwaywall. The airway wall will deflect and become displaced until the deviceis withdrawn. If the tissue becomes tented there remains a significantamount of potential energy placed by the device onto the airway wall.The potential energy may unexpectedly becomes realized, when the deviceeventually punctures the airway, which may cause the device to suddenlyplunge into the parenchyma to an unintended depth. Plunging may in turncause unintended damage to the patient. A depth limiting feature 654 mayovercome this problem.

Variations of the invention include a depth limiting feature that mayprevent inadvertent advancement of the device when creating the channel.One example of this may be a circular tube 654 placed over the deviceand set at a fixed distance (e.g. 10 mm) from the distal tip of thepiercing member, proximal to the balloon, as shown in FIG. 4J. If thedevice does tent and plunge into the airway wall the front face of thetube may halt the plunging effect by acting as a barrier. Anotherexample would be a secondary balloon, proximal to the channel expansionballoon, placed in a similar position to the circular tube as describedabove. Another example would be a folding basket formed from the outerlumen of the device, or constructed from wire.

As shown in FIG. 4K, variations of the invention may include a distalcollar 650 on the distal portion of the piercing member 604 to preciselylimit the maximum extension and retraction of the piercing member 604.The distal collar 650 would be attached to the piercing member andtravel between two set collar stops 652 which are attached to the lumen656 the piercing member travels in. This feature has multiple benefits;first, it has the safety setting a maximum distance for the piercingmember to extend, around 2-3 mm has been found to be sufficient in mostcases. Thus, the maximum penetration of the piercing member 604 islimited which may prevent unintentional damage to the lung tissue.

The collar 650 protects the bronchoscope by preventing deflection of thedistal tip. Deflection can take place when there is a significant amountof gap between the inner sheath 622 and the distal tip of the piercingmember in the retracted mode. When the device is being maneuveredthrough a bronchoscope in a torturous configuration, the lumen 656 candeflect while the stiffer piercing member will not, and thus thepiercing member may pierce through the deflected lumen 656 andsubsequently into the bronchoscope. By setting a small gap (e.g. <1 mm)this deflection may be eliminated, and the scope protected.

The collar 650 also allows the piercing member to be reliably extended.It was found that when a similar feature was placed at the proximalsection of the device the piercing member could not reliably be extendedto a set distance beyond the distal tip. This is because when in atorturous configuration the outer sheath 620 of the device may have atendency to stretch or compress. As a result the tubing may stretch tosuch a degree that when the piercing member is filly extended it stillmay not fully extend past the distal tip of the lumen 656. By locatingthe collar 650 in the distal portion of the lumen 656 (e.g. less than 2inches from the distal tip) the stretching or compression is minimizedor eliminated.

Conduit Deployment Devices and Methods

FIGS. 5A-5C illustrate a way to deploy a conduit in a channel. Referringto FIG. 5A, a delivery device 400 is loaded with a conduit 200. Anaccess scope-type device 404 (e.g., an endoscope, a bronchoscope, orother device) may optionally be used to place the delivery device 400into a collateral channel 112. A guide wire 402 may be used to place thedelivery device 400 into the collateral channel 112. The guide wire 402may be a conventional guide-wire or it may simply be comprised of asuper-elastic material. The use of a guide wire is optional as theinvention contemplates placement of the conduit 200 using only thedelivery device 400.

FIG. 5A also illustrates articulation (or bending) of the deliver device400 to access the collateral channel 112. However, the invention alsocontemplates articulation of the access device 404. The access device404 may be articulated such that the delivery device 400 may advancestraight into the collateral channel 112. Accordingly, the deliverydevice 400 may exit straight from the access device 404 or it may bearticulated into the opening.

FIG. 5B illustrates deployment of the conduit 200. In particular,balloon member 406 is shown in an expanded state resulting in (1) theconduit's center section being radially expanded and (2) the conduit'sextension members being outwardly deflected such that opposing extensionmembers sandwich portions of the tissue wall 422. Diametric-controlmembers 424 are also shown in this figure. The diametric orcenter-control segments limit the center section's radial expansion. Inthis manner, conduit 200 is securely placed in the channel to maintain apassageway through the airway wall 422.

FIG. 5C illustrates the deployed conduit 200 once the delivery device400 is removed from the site. It should be noted that dilation of thecollateral channel or opening 112 may be performed by mere insertion ofthe conduit 200 and/or delivery device 400.

It should be noted that deployment of conduits is not limited to thatshown in FIGS. 5A-5C, instead, other means may be used to deploy theconduit. For example, spring-loaded or shape memory features may beactuated by mechanical or thermal release and unlocking methods.Additionally, mechanical wedges, lever-type devices, scissors-jackdevices, open chest surgical placement and other techniques may be usedto deploy the conduit. Again, the conduit 200 may be comprised of anelastic or super-elastic material which is restrained in a reducedprofile for deployment and expands to its deployed state upon mechanicalactuator or release.

In one additional variation of the invention, as shown in FIGS. 5D, aconduit 201 may be deployed within a second structure such as a secondconduit or stent. Such an approach may be used to increase retention ofthe conduits within the channel as well as prevent closing of thechannel. For example, an initial conduit 200 or stent may be deployedwithin the channel 112. This first conduit or stent may have certainproperties that make it more acceptable to implantation within the bodywithout generating an aggressive tissue healing response. For instance,the stent may be a drug eluting stent, or the conduit may be constructedfrom a bio-compatible metal without any additional tissue barrier. Oncethe initial stent or conduit is placed within the channel 112 a secondconduit may be deployed within the first conduit. As shown in FIG. 5D, afirst conduit 200 (or stent) is placed within the channel 112. FIG. 5Dillustrates a second conduit 201 advanced towards the first conduit 200.FIG. 5E illustrates the second conduit 201 deployed within the firstconduit 200. The second conduit 201 may have additional properties thatpermit the channel to remain patent. For example, the second conduit 201my have a tissue barrier as discussed above, or other construction thatgenerates an aggressive healing response within the lung. Therefore, thefirst conduit 200, being more conducive to implantation, will serve toanchor both conduits 200, 201 as the tissue either does not grow, or itgrows around the outer conduit 200. The second conduit, for example, mayhave a tissue barrier placed thereon. Once the second conduit 201 isdeployed within the first conduit 200, the tissue barrier of the secondconduit 201 will prevent tissue from growing through the stentstructure. It should be noted that the structure of a conduit within aconduit may be incorporated into a single composite structure.

In use, the conduit 200 is deployed with the distal side towards theparenchymal tissue 460 while the proximal side remains adjacent or inthe airway 450. Of course, where the proximal and distal extensionmembers are identical, the conduit may be deployed with either sidetowards the parenchymal tissue.

FIGS. 6A-6B illustrate another example of deploying a conduit 500 in achannel 510 (or opening) created in a tissue wall 520. Referring to FIG.6A, a delivery tool 530 carrying a deployable conduit 500 is insertedinto the channel 510. The delivery tool 530 is extended straight from anaccess catheter 540 such that the delivery tool forms an angle

with the tissue wall 520. It is to be understood that while the tissuewall of airway 522 is shown as being thin and well defined, the presentinvention may be utilized to maintain the patency of channels andopenings which have less well defined boundaries. The delivery tool isfurther manipulated until the conduit is properly positioned which isdetermined by, for example, observing the position of a visualizationmark 552 on the conduit relative to the opening of the channel 510.

FIG. 6B illustrates enlarging and securing the conduit in the channelusing an expandable member or balloon 560. The balloon 560 may beradially expanded using fluid (gas or liquid) pressure to deploy theconduit 500. The balloon may have a cylindrical shape (or another shapesuch as an hourglass shape) when expanded to 1.) expand the centersection and 2.) deflect the proximal and distal sections of the conduitsuch that the conduit is secured to the tissue wall 520. During thisdeployment step, the tissue wall 520 may distort or bend to some degreebut when the delivery tool is removed, the elasticity of the tissuetends to return the tissue wall to its initial shape. Accordingly, theconduits disclosed herein may be deployed either perpendicular to (ornon-perpendicular to ) the tissue wall.

FIG. 7A illustrates another variation of deploying a conduit 200 into anopening 112. In some variations of the invention, prior to deployment ofthe conduit 200, the channel 112 may have a diameter or size that mayrequire an additional dilation or expansion of the channel 112 forproper deployment of the conduit 200. For example, the channel 112 maybe created by a piercing member, as described above, where the channel112 nearly closes upon removal of the piercing member. However, thedevices and method described herein are not limited to channels 112 ofany particular size. The channels may in fact be larger than a diameterof the conduit 200 in its un-deployed state.

In any case, after creation of the channel 112 the surgeon may advance aballoon catheter 630 containing a conduit 200 towards the site of theopening 112. The variation of the balloon catheter 630 depicted in thefigure also includes a guide body 632. Because the opening 112 may bedifficult to locate, the guide body 632 may serve various functions toassist in locating the opening 112 and placing the conduit 200. Forexample, as shown in FIG. 7A, the guide body 632 may have a roundedfront surface. This allows probing of the catheter 630 against theairway 100 wall to more easily locate the opening 112. The roundedsurface of the guide body 632 will not drag on the airway tissue.

As shown in FIG. 7B, once inserted into the opening 112, the guide body632 provides an additional function of temporarily anchoring the device630 within the opening 112. The ability to temporarily anchor the device630 into the opening 112 may be desirable due to the natural tidalmotion of the lung during breathing. The increased surface area of theguide body 632 requires increased resistance upon remove the guide body632 from the opening 112. Such a feature lessens the occurrence ofunintended removal of the device from the site as the lung tissue moves.As shown in FIG. 7B, after insertion into the airway 100 wall, a portionof the guide body 632 serves as a resistance surface to provide thetemporary anchoring function. Additional variations of the guide body632 are shown below.

FIGS. 8A-8F illustrate additional variations of guide bodies 632 for usewith the present invention. As shown, the guide body 632 is located onthe distal end of the balloon catheter 630. The guide body 632 will havea front surface 634 that is preferably smooth such that it can easily bemoved over the airway wall. Proximal to the front surface 634, the guidebody 632 will have at least one resistance surface 636 which is definedas an area that causes increased resistance upon removal of the guidebody 634 from the airway wall. As shown, the resistance surface 636 willbe adjacent to an area of reduced diameter 638 to which allows the guidebody 632 to nest within the opening 112 in the airway wall. The guidebody 632 may have any number-of shapes as shown in the figures.

FIG. 8F illustrates another variation of a guide body 632 having aresistance surface 636 which comprises an area of increased surfaceroughness such that the surface will drag upon the airway wall or tissuesurrounding the channel 112. Such a feature may be combined with thevariations of the guide members provided above.

The balloon catheters 630 of the present invention may include adilating member between the guide body 632 and balloon 614. In thevariation shown in FIG. 8A, the dilating member comprises a taperedsection. However, the invention is not limited as such. For example, thedilating member may comprise a second inflatable balloon, or otherexpanding device. The dilating members may also be retractable withinthe elongate shaft.

FIGS. 9A and 9B depict cross sections of examples of a balloon catheter630 having a guide body 632 that includes a lumen 642 which terminatesat a surface of the guide body 632. The lumen 642 may be used forsuction, irrigation, or deliver bio-active substances, etc. The catheter630 may also have an additional lumens 646, 646, 648 as shown, forinflation of the balloon 614 and for additional suction 644, and forcommunication with the guide body lumen 642. As shown in FIG. 8B, thelumen may also be used to advance a piercing member 604 to the airwaywall to create the channel 112.

Any of the balloons described herein may be distensible balloons (e.g.,they assume a predetermined shape upon expansion) or elastic balloons(e.g., simply expand). Use of a distensible balloon permits control indilating the opening 112 or placement of the conduit.

All publications, patent applications, patents, and other referencesmentioned herein are incorporated by reference in their entirety. To theextent there is a conflict in a meaning of a term, or otherwise, thepresent application will control. Although the foregoing invention hasbeen described in some detail by way of illustration and example forpurposes of clarity of understanding, it will be readily apparent tothose of ordinary skill in the art in light of the teachings of thisinvention that certain changes and modifications may be made theretowithout departing from the spirit or scope of the appended claims. It isalso contemplated that combinations of the above describedembodiments/variations or combinations of the specific aspects of theabove described embodiments/variations are within the scope of thisdisclosure.

EXAMPLE Implant

Implants comprising stainless steel mesh frame fully encapsulated with acomposition comprising silicone (as described below) and paclitaxel wereimplanted in several canine models. Visual observation indicated that,on average, the passage through the implants of the present inventionremained unobstructed and were associated with significantly reducedfibrotic and inflammatory responses, in canine models, at a considerablyhigher rate than an implant without any drug adjunct or coronary drugeluting stents (as shown in FIG. 12).

The composition comprised approximately a 9% paclitaxel to siliconeratio with approximately 400 micrograms of paclitaxel per implant.Measurements found that approximately 30% of the paclitaxel releasedafter 60 days. In general, for implants with the paclitaxel/siliconecomposition, observations of chronic inflammation, epithelial metaplasiaand fibrosis were all very mild.

For paclitaxel as the bioactive substance, polymers with solubilityparameters between 5-25 (MPa) {circumflex over (0 )}½ were believed toprovide sufficient elution rates. The polymer used in the example devicehas good diffusivity for lipophilic drug (such as paclitaxel) becausethe side methyl group on the silicone may be substituted with morelipophilic hydrocarbon molecules containing vinyl group or groups inaddition polymerization by platinum catalyst.

The composition for the example may be as follow: polymer part:polydimethylsiloxane, vinyldimethyl terminated, any viscosity; and/orpolydimethylsiloxane, vinylmonomethyl terminated, any viscosity. Thecross-linker part: polydimethylsiloxane, any viscosity; and orpolymonomethylsiloxane, any viscosity. Platinum catalyst part and/orcross-linker part: platinum; and/orplatinum-divinyltetramethyldisiloxane complex in xylene, 2-3% Pt; and/orplatinum-divinyltetramethyldisiloxane complex in vinyl terminatedpolydimethylsiloxane, 2-3% Pt; and/orplatinum-divinyltetramethyldisiloxane complex in vinyl terminatedpolydimethylsiloxane, ˜1% Pt; platinum-Cyclovinylmethylsiloxane complex,2-3% Pt in cyclic vinyl methyl siloxane.

These components may be combined in different ratios to make thepolymer. The hydrocarbon side chain off the silicone back bone makesthis polymer system unique and may result in a “zero-order”-like releaseprofile. The amount of vinyl siloxane cross-linker may determine therate of the drug release and diffusivity of the polymer to the drug.There are other types of polydimethylsiloxanes such as: trimethylsiloxyterminated polydimethylsiloxane in various viscosities, (48-96%)dimethyl (4-52%) diphenylsiloxane copolymer in various viscosities,dimethylsiloxane-ethylene oxide copolymer, dimethyl diphenylsiloxanecopolymer, polymethylhydrosiloxane, trimethylsilyl terminated at variousviscosities, (30-55%) methyldro-(45-70%) dimethylsiloxane copolymer atvarious viscosities, polymethylphenylsiloxane, polydimethylsiloxanesilanol terminated at various viscosities, polydimethylsiloxaneaminopropyldimethyl terminated at various viscosities. For paclitaxel arelease profile was found to be acceptable with a polymer systemconsisting of polydimethylsiloxane vinyl terminated at various viscosityand a range of platinum-mono, di, tri and/or tetramethyldisiloxanecomplex.

1. A hole-making catheter for creating and dilating an opening withintissue, the catheter comprising; an elongate shaft having a proximalportion and a distal portion, and at least one lumen extending throughthe proximal end; a nondistensible balloon having an interior in fluidcommunication with the lumen, the nondistensible balloon located on thedistal portion of the elongate shaft,; and a piercing member located atthe distal portion of the elongate shaft, the piercing member beingextendable and retractable within the elongate shaft.
 2. The catheter ofclaim 1, where the piercing member comprises a wire extending throughthe elongate shaft where the distal end of the wire is sufficientlysharp to pierce tissue.
 3. The catheter of claim 1, further comprising asecond lumen extending through the piercing member.
 4. The catherte ofclaim 1, further comprising an elongate member adapted to the pirecingmember and slidably movable withing the elongate shaft.
 5. The catheterof claim 4, further comprising a PTFE coating around the elongatemember.
 6. The catheter of claim 4 further comprising a closed coiledspring around the elongate member.
 7. The catheter of claim 4 furtherwhere the elongate member and the piercing member have a continuouslumen extending therethrough.
 8. The hole-making catheter of claim 1,where the elongate shaft has sufficient flexibility to advance through afully articulated bronchoscope.
 9. The hole-making catheter of claim 1,where the balloon comprises a proximal balloon end, a distal balloonend, and a center balloon section, where upon inflation of the balloon,the proximal and distal balloon ends form a diameter greater than adiameter of the center balloon section.
 10. The catheter of claim 1,further comprising a depth limiter stop located on the distal portion ofthe elongate shaft, proximal to the balloon and larger in workingdiameter than the uninflated balloon, which resists the maximumpenetration of the catheter into tissue.
 11. The catheter of claim 10,where the depth limiter stop is a tube.
 12. The catheter of claim 11,where the tube extends to the proximal end of the elongate member. 13.The catheter of claim 10, where the depth limiter stop is a secondballoon.
 14. The catheter of claim 10, where the depth limiter stop is afolding basket.
 15. The catheter of claim 10, where the depth limiterstop is formed into the elongate shaft.
 16. The catheter of claim 1,further comprising a collar located on the distal portion of thepiercing member, which limits the maximum extension and retraction ofthe piercing member.
 17. A hole-making catheter for creating anddilating an opening within tissue, the catheter comprising; an elongateshaft having a proximal portion and a distal portion, and at least onelumen extending through the proximal end; a balloon having proximal endand a distal end and an interior in fluid communication with the lumen,the balloon located on the distal portion of the elongate shaft, and apiercing member located at the distal portion of the elongate shaft, thepiercing member being slidable within the elongate shaft such that adistal end of the piercing member may extend distal to a distal end ofthe balloon and, upon sliding of the piercing member, the distal end ofthe balloon may be distal to the distal end of the piercing member. 18.The hole-making catheter of claim 17, where the working diameter of theballoon is less than a diameter of the distal end of the elongate shaft.19. The hole-making catheter of claim 17, where the balloon extends outof the distal end of the elongate shaft.
 20. The hole-making catheter ofclaim 17 where the balloon is fixed relative to the elongate shaft. 21.The hole-making catheter of claim 17 where the balloon comprises tubewithin the balloon, where the piercing member is slidably located withinthe tube and the balloon may deflate onto the tube.
 22. The hole-makingcatheter of claim 17 where the balloon is a nondistensible balloon. 23.The hole-making catheter of claim 17 further comprising a second lumenextending through the piecing member.
 24. A implant delivery system fordeploying the implant within a wall of tissue, the system comprising; anelongate shaft having a distal portion, a proximal end, a distal end, atleast one lumen extending through the proximal end; a balloon memberhaving an interior in fluid communication with the lumen, the balloonmember located on the distal portion of the elongate shaft; a piercingmember distally located to the distal end of the elongate shaft withinthe second lumen, the solid piercing member having a sharpened distalend adapted to penetrate tissue; and an expandable implant located aboutthe balloon member.
 25. The implant delivery system of claim 24, wherethe piercing member is extendable and retractable.
 26. The implantdelivery system of claim 24, where the piercing member is formed fromone wire extending into the proximal end of the elongate shaft.
 27. Theimplant delivery system of claim 26, where the wire is constructed fromnitinol.
 28. The implant delivery system of claim 24, further comprisinga second lumen continuous within the piercing member.
 29. The catheterof claim 24, further comprising a PTFE coating around the piercingmember.
 30. The catheter of claim 24, further comprising a closed coiledspring around the pushing member.
 31. The catheter of claim 24, furthercomprising a closed coil spring connected to the outside of the pushingmember.
 32. The implant delivery system of claim 24, where the elongateshaft and piercing member has sufficient flexibility to advance througha fully articulated bronchoscope.
 33. The implant delivery system ofclaim 24, where the balloon member is a non-distensible balloon.
 34. Theimplant delivery system of claim 24, where the balloon member is adistensible balloon.
 35. The implant delivery system of claim 24, wherethe balloon member comprises a proximal balloon end, a distal balloonend, and a center balloon section, where upon inflation of the balloon,the proximal and distal balloon ends form a diameter greater than adiameter of the center balloon section.
 36. The implant delivery systemof claim 24; where the implant is a different color or texture from theballoon member thereby making the implant optically distinguishable fromthe balloon when viewed through an endoscope.
 37. The implant deliverysystem of claim 36, where the implant is white.
 38. The implant deliverysystem of claim 36, where the balloon member comprises a colored sheathover a balloon.
 39. The implant delivery system of claim 39, where thesheath is blue.